Marfan Syndrome Decreases Ca<sup>2+</sup> Wave Frequency and Vasoconstriction in Murine Mesenteric Resistance Arteries without Changing Underlying Mechanisms
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Bibliographic record
Abstract
<i>Background/Aims:</i> Vascular smooth muscle in Marfan syndrome, a connective tissue disorder caused by mutations in <i>FBN1</i> encoding fibrillin-1, is associated with decreased tonic contraction. As Ca<sup>2+</sup> waves are tightly associated with vasoconstriction, we hypothesized decreased tonic contraction in Marfan syndrome is due to aberrant Ca<sup>2+</sup> wave signaling. <i>Methods:</i> Isometric force and intracellular Ca<sup>2+</sup> were measured from second-order mesenteric arteries from mice heterozygous for the <i>Fbn1</i> allele encoding a cysteine substitution (<i>Fbn1</i><sup>C1039G/+</sup>). <i>Results:</i> Phenylephrine concentration-dependently induced tonic contraction associated with sustained repetitive oscillations in intracellular [Ca<sup>2+</sup>] in both control and Marfan vessels, although Marfan vessels displayed significantly decreased Ca<sup>2+</sup> wave frequency and decreased number of cells exhibiting waves. Inhibition of sarcoplasmic reticulum Ca<sup>2+</sup> re-uptake by cyclopiazonic acid abolished Ca<sup>2+</sup> waves, dramatically decreasing tonic contraction. Nifedipine significantly reduced Ca<sup>2+</sup> wave frequency and tonic contraction, while the nifedipine-insensitive component was abolished by SKF-96365. Ca<sup>2+</sup> waves and tonic contraction were abolished by 2-aminoethoxydiphenylborate, but were unaffected by ryanodine or tetracaine. <i>Conclusion:</i> Phenylephrine-induced Ca<sup>2+</sup> waves underlie tonic contraction in resistance-sized mesenteric arteries and appear to be produced by repetitive cycles of regenerative Ca<sup>2+</sup> release from the sarcoplasmic reticulum. Decreased frequency of Ca<sup>2+</sup> waves in Marfan syndrome appears to be responsible for reduced tonic contraction.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it